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Ivermectin's neuroprotective effects decrease with prolonged use after cerebral ischemia/reperfusion
Sevda Rezaei1, Shabnam Babataheri1, Hamid Soraya2
1Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.
Metabolic Brain Disease
|June 25, 2025
Summary
Prolonged administration of ivermectin (IVM) did not improve cognitive function or infarct size after stroke in rats. However, it reduced markers of inflammation and improved motor coordination, suggesting varied effects based on drug regimen.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Ivermectin (IVM) is an FDA-approved antiparasitic drug with potential neuroprotective properties.
- Previous studies indicated neuroprotection with short-term ivermectin administration post-cerebral ischemia/reperfusion (IR).
- The effects of prolonged ivermectin administration on neurological disorders, particularly cerebral IR and neutrophil extracellular traps (NETs), require further investigation.
Purpose of the Study:
- To determine if prolonged ivermectin administration maintains neuroprotective effects in a rat model of cerebral IR.
- To evaluate the impact of sustained ivermectin treatment on NET formation and related inflammatory markers.
- To assess ivermectin's effects on cognitive function, motor skills, and infarct size following cerebral IR.
Main Methods:
- A transient global cerebral IR model was induced in rats by occluding carotid arteries.
- Ivermectin (2 mg/kg/day) was administered intraperitoneally for 7 consecutive days, starting 1 hour post-ischemia.
- Evaluated outcomes included brain infarct size, blood parameters, memory, motor coordination, myeloperoxidase activity, and citrullinated histone H3 (H3cit) levels.
Main Results:
- Seven-day ivermectin administration did not improve memory, learning, blood parameters, or cerebral infarct size.
- A significant reduction (25.4%) in citrullinated histone H3 protein levels was observed.
- Myeloperoxidase activity decreased significantly (P=0.017), and balance and motor coordination improved (P=0.017, P=0.024).
Conclusions:
- Prolonged ivermectin administration may alter or diminish its neuroprotective effects compared to shorter regimens.
- Sustained ivermectin treatment impacts inflammatory markers and motor function, but not cognitive recovery or infarct size in this model.
- The therapeutic efficacy of ivermectin in neurological disorders may be dependent on the specific drug administration schedule and duration.
